A Convenient Synthesis of 4-Oxo-4H-quinolizines

Abstract

By reacting o-substituted picolines (1 j ( o r their synthetic equivalents) with R,R-dichlaroprapenal5 ( $ 1 ( o r their synthetic equivalents) substituted 1-(2-pyridylj-4.4-dichloro-1,3-butadienes ( 6 j were produced.Compounds ($1 were smoothly cyclized to the corresponding 4-om-4H-quinolizines (8) bearing substituents in the 1 and/or 3 positions.4-0x0-4H-quinalizines are of general interest in view of the potential use of 1 compounds containing their nucleus as biologically active compounds.Several general routes leading to this heterocyclic system have been described in the literature 2-7 and some work had been done to clarify the behaviour of oxoquinolizines with respect to electrophilic reagents.3'8'9 As a part of a work directed to the obtention of some substituted 4-0x0-4H-quinolizines we have developed a convenient synthetic procedure which involves the condensation of derivatives of 2-picaline with 8,R-dichloroacroleins or their precursors and the cyclization of the condensation products.RESULTS AND DISCUSSION Reaction of ethyl (2-pyridy1)acetate I and (2-pyridyl jacetonitrile (1:).Pespectively, with an equimolecular amount of 3-ethoxy-1,1.3-trichlorapropene(?%I in 95% acetic acid at 0°C and reacting at room temperature for 12-20 h resulted in the formation of the corresponding ethyl 2-12-pyridylI-5,5-dich10ro- 2,4-pentadienoate (6bj and 2-(2-pyridy1)-5.5-dichloro-2,4-pentadienonitrile(%$).% % respectiv?ly.Starting from ( 2 ) and 2-nitromethylpyridine ( 1 % : ) a mixture of 1-( 2-pyridyl I-4.4-dichloro-1-nitro01 , 3 -b t a d i ( 6d ) and its cyclization product ".".(El was formed.Pure ($5) was obtained by chromatografic separation on 21, 3278 (